Integrative metabolomic-proteomic analysis uncovers a new therapeutic approach in targeting rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory condition that, despite available approaches to manage the disease, lacks an efficient treatment and timely diagnosis. Using the most advanced omics technique, metabolomics and proteomics approach, we explored varied metabolites and proteins to identify unique metabolite-protein signatures involved in the disease pathogenesis of RA.

Methods: Untargeted metabolomics (n = 20) and proteomics (n = 60) of RA patients' plasma were carried out by HPLC/LC-MS/MS and SWATH, respectively and analyzed by Metaboanalyst.

Exploring the impact of 2-hydroxyestradiol on heme oxygenase-1 to combat oxidative stress in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation driven by complex signaling pathways. Recent therapeutic approaches focus on small molecules targeting intracellular signaling to address specific physiological aspects of the disease. Previously we identified a small molecule, 2-hydroxyestradiol (2-OHE2), an inhibitor of TNF-α by an in-silico study.

Optimizing Hierarchical Condition Category-Risk Adjustment Factor Management in Population Health Using Rapid Process Improvement Methods.

Centers for Medicare & Medicaid Services provides reimbursement through Hierarchical Condition Category (HCC) coding. Medical systems strive toward risk adjustment optimization, often implementing costly chart review processes. Previously, our organization implementing countermeasures through workflows was complex and performed in silos.

Clo-miR-14: a medicinally valued spice-derived miRNA with therapeutic implications in rheumatoid arthritis.

Plant microRNAs (miRNA) are regularly consumed orally along with diet, gaining attention for their RNA-based drug potential because of their ability to regulate mammalian gene expression specifically at the post-transcriptional level. Medicinally valued plants are well known for their anti-inflammatory property; however, the contribution of their miRNA in managing inflammation has been less studied. We investigated miRNA from four medicinally valued regularly consumed spices, and validated one of the most potential miRNA 'Clo-miR-14' for its thermal stability, and absorption in the plasma samples of RA patient's by RT-PCR.

Chronic disease management via modulation of cellular signaling by phytoestrogen Bavachin.

The emergence of chronic diseases, particularly cancers, cardiovascular, and bone disorders, presents a formidable challenge, as currently available synthetic drugs often result in significant side effects and incur higher costs. Phytoestrogen Bavachin, present in the Psoralea corylifolia L. plant, represents structural and functional similarity to mammalian estrogen and has recently attracted researchers for its medicinal properties.

The Effect of an AI-Based, Autonomous, Digital Health Intervention Using Precise Lifestyle Guidance on Blood Pressure in Adults With Hypertension: Single-Arm Nonrandomized Trial.

Background: Home blood pressure (BP) monitoring with lifestyle coaching is effective in managing hypertension and reducing cardiovascular risk. However, traditional manual lifestyle coaching models significantly limit availability due to high operating costs and personnel requirements. Furthermore, the lack of patient lifestyle monitoring and clinician time constraints can prevent personalized coaching on lifestyle modifications.

Functional Significance of miR-4693-5p in Targeting HIF1α and Its Link to Rheumatoid Arthritis Pathogenesis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint inflammation and destruction with an unknown origin. Our study aims to elucidate the molecular mechanism behind HIF1α overexpression in RA. Dysregulated miRNA expressions are known to influence gene behavior, thereby enhancing cell proliferation, inflammation, and resistance to apoptosis, contributing to RA development.

Targeting TNF-α-induced expression of TTR and RAGE in rheumatoid arthritis: Apigenin's mediated therapeutic approach.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease induced by TNF-α, which increases fibroblast-like synoviocytes inflammation, resulting in cartilage destruction. The current work sought to comprehend the pathophysiological importance of TNF-α stimulation on differential protein expression and their regulation by apigenin using in-vitro and in-vivo models of RA.

Methods: The human RA synovial fibroblast cells were stimulated with or without TNF-α (10 ng/ml) and treated with 40 μM apigenin.

Mitochondrial functioning in Rheumatoid arthritis modulated by estrogen: Evidence-based insight into the sex-based influence on mitochondria and disease.

Alteration of immune response and synovium microvasculature in Rheumatoid arthritis (RA) progression has been suggested to be associated with mitochondrial functioning. Mitochondria, with maternally inherited DNA, exhibit differential response to the female hormone estrogen. Various epidemiological evidence has also shown the prominence of RA in the female population, depicting the role of estrogen in modulating the pathogenesis of RA.

Evaluation of -quinoline alkaloids by RP-HPLC-PDA in different species collected from Western Himalayan Region.

The genus has high significance in Indian and other traditional systems of medicine due to the presence of -quinoline alkaloids. This study was conducted to record the metabolic variation in eight spp. collected from the Western Himalayan region.

Anti-rheumatic potential vis-à-vis aconitine and hypaconitine content analysis in different Aconitum spp. from Sikkim Himalayas (India).

Aconitum spp. are important medicinal plants mentioned in Ayurveda as Ativisa or Vatsanabha. The present study aims to evaluate anti-rheumatic potential in seven Aconitum species and correlation with aconitine and hypaconitine content.

CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker.

Lymphocyte activation gene 3 protein (LAG3) is an inhibitory receptor that is upregulated on exhausted T cells in tumors. LAG3 is a major target for cancer immunotherapy with many anti-LAG3 antibodies in clinical trials. However, there is no structural information on the epitopes recognized by these antibodies.

Interrelated grid of non-coding RNA: An important aspect in Rheumatoid Arthritis pathogenesis.

Inflammation and autoimmunity are the root cause of rheumatoid arthritis, a destructive disease of joints. Multiple biomolecules are involved in the pathogenesis of RA and are related to various events of molecular biology. RNA is a versatile biomolecule, playing numerous roles at structural, functional, and regulatory stages to maintain cellular homeostasis.

Anti-inflammatory potential of selective small compounds by targeting TNF-α & NF-kB signaling: a comprehensive molecular docking and simulation study.

Tumor necrosis factor alpha (TNF-α) is the major cause of inflammation in autoimmune diseases like rheumatoid arthritis (RA). It's mechanisms of signal transduction through nuclear factor kappa B (NF-kB) pathway via small molecules such as metabolite crosstalk are still elusive. In this study, we have targeted TNF-α and NF-kB through metabolites of RA, to inhibit TNF-α activity and deter NF-kB signaling pathways, thereby mitigating the disease severity of RA.

An update on the taxonomy of (Bor) G.Singh and its allies (Poaceae, Agrostidinae): morphometrics and micro-morphology.

, previously considered to be a poorly known species, has been reassessed taxonomically. It is a member of - complex and may be segregated by morphological characters such as the presence of pilose hairs on adaxial surface of leaf blades, spreading panicle branches, filiform awn and nerve prolongation of lemma. Besides, the micromorphology of adaxial surface of leaf blades, dorsal surface of glume and lemma differentiates from its allies, and .

Quinolinyl β-enaminone derivatives exhibit leishmanicidal activity against Leishmania donovani by impairing the mitochondrial electron transport chain complex and inducing ROS-mediated programmed cell death.

Objectives: Previously, a series of side chain-modified quinolinyl β-enaminones was identified to possess significant activity against chloroquine-sensitive or -resistant Plasmodium falciparum and Brugia malayi microfilariae. The present study evaluates in vitro and in vivo activity of the series against Leishmania donovani and reports their mode of action.

Methods: The in vitro activity of 15 quinolinyl β-enaminone derivatives against Leishmania promastigotes and amastigotes was assessed by luciferase assay.

Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity.

Antigen recognition by the T cell receptor (TCR) of CD4 T cells can be greatly enhanced by the coreceptor CD4. Yet, understanding of the molecular mechanism is hindered by the ultra-low affinity of CD4 binding to class-II peptide-major histocompatibility complexes (pMHC). Here we show, using two-dimensional (2D) mechanical-based assays, that the affinity of CD4-pMHC interaction is 3-4 logs lower than that of cognate TCR-pMHC interactions, and it is more susceptible to increased dissociation by forces (slip bond).

Unmet needs for food, medicine, and mental health services among vulnerable older adults during the COVID-19 pandemic.

Objective: To examine sociodemographic factors associated with having unmet needs in medications, mental health, and food security among older adults during the COVID-19 pandemic.

Data Sources And Study Setting: Primary data and secondary data from the electronic health records (EHR) in an age-friendly academic health system in 2020 were used.

Study Design: Observational study examining factors associated with having unmet needs in medications, food, and mental health.

Epitope Mapping of Therapeutic Antibodies Targeting Human LAG3.

Lymphocyte activation gene 3 protein (LAG3; CD223) is an inhibitory receptor that is highly upregulated on exhausted T cells in tumors and chronic viral infection. Consequently, LAG3 is now a major immunotherapeutic target for the treatment of cancer, and many mAbs against human (h) LAG3 (hLAG3) have been generated to block its inhibitory activity. However, little or no information is available on the epitopes they recognize.

Nocturnal Respiratory Rate Dynamics Enable Early Recognition of Impending Hospitalizations.

The days and weeks preceding hospitalization are poorly understood because they transpire before patients are seen in conventional clinical care settings. Home health sensors offer opportunities to learn signatures of impending hospitalizations and facilitate early interventions, however the relevant biomarkers are unknown. Nocturnal respiratory rate (NRR) is an activity-independent biomarker that can be measured by adherence-independent sensors in the home bed.